# Acute Kidney Injury in Diabetes

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2020 · $431,906

## Abstract

Project Summary
Comorbid conditions, such as diabetes, increase the severity of acute kidney injury (AKI) and prevents
injured kidneys from recovery, resulting in poor prognosis. However, the mechanism underlying the
heightened AKI sensitivity in diabetes is largely unknown. We and others recently verified the AKI
sensitivity in diabetes and suggested the involvement of inflammation and p53. In diabetic kidneys, our
preliminary studies further demonstrated the inactivation of autophagy, a renoprotective mechanism.
Mechanistically, we have identified the down-regulation of ULK1, a key autophagy initiator, as a
common feature in diabetic kidneys and high glucose-treated kidney cells. ULK1 down-regulation is not
associated with mRNA decrease or proteosomal degradation, suggesting the involvement of novel
mechanisms. Bioinformatics analysis suggested the targeting of ULK1 by miR-214, a microRNA
induced in diabetic kidneys. Notably, our preliminary data further suggested a role of p53 in miR-214
induction. Based on these findings, we hypothesize that: miR-214 is induced via p53 in diabetes and
upon induction, miR-214 represses ULK1 resulting in autophagy impairment, which contributes to AKI
sensitivity in diabetes. Specifically, we will determine the role of p53 in miR-214 induction in diabetic
kidneys, delineate miR-214 targeting/repression of ULK1, and elucidate autophagy impairment as a key
to AKI sensitivity in diabetes. Completion of this project will delineate a novel pathway of p53/miR-
214/ULK1 that leads to autophagy impairment and AKI sensitivity in diabetes. As a result, it may
identify miR-214 and autophagy as novel therapeutic targets for AKI therapy and prevention in diabetic
patients.

## Key facts

- **NIH application ID:** 10019503
- **Project number:** 5R01DK058831-18
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Zheng Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $431,906
- **Award type:** 5
- **Project period:** 2001-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019503

## Citation

> US National Institutes of Health, RePORTER application 10019503, Acute Kidney Injury in Diabetes (5R01DK058831-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019503. Licensed CC0.

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